To evaluate real-world effectiveness and safety of adjuvant disitamab vedotin plus PD-1 blockade (ADC+ICI) versus gemcitabine/cisplatin (GC) in high-risk upper tract urothelial carcinoma after radical nephroureterectomy.
This single-center, two-stage observational study enrolled 421 patients with study-defined high-risk upper tract urothelial carcinoma. Cohort A evaluated adjuvant GC versus surgery alone using propensity score matching. Cohort B compared adjuvant GC with ADC+ICI using overlap weighting, with ECOG performance status and three-level HER2 IHC category included in covariate adjustment. Overall survival (OS), conventional disease-free survival (DFS), non-intravesical progression-free survival (PFS), intravesical recurrence-free survival (IVRFS), safety, and exploratory HER2-stratified outcomes were assessed.
In Cohort A, adjuvant GC was associated with improved OS after matching. In Cohort B, 48 patients received GC and 53 received ADC+ICI. After overlap weighting, baseline covariates were well balanced. ADC+ICI was not associated with a significant OS improvement versus GC (HR 0.47, 95% CI 0.12-1.89; P = 0.287; FDR-adjusted P = 0.403). Directionally favorable associations were observed for conventional DFS (HR 0.32, 95% CI 0.11-0.96; nominal P = 0.043; FDR-adjusted P = 0.172), non-intravesical PFS (HR 0.32, 95% CI 0.09-1.18; P = 0.086), and IVRFS (HR 0.21, 95% CI 0.04-1.09; P = 0.063). HER2 IHC 2+/3+ tumors showed exploratory favorable DFS/PFS signals. Grade ≥3 treatment-related adverse events were similar between groups.
Adjuvant ADC+ICI showed comparable short-term OS and directionally favorable DFS/PFS trends versus GC, with a distinct toxicity profile. These findings are hypothesis-generating and require prospective validation.
Frontiers in immunology. 2026 Jun 16*** epublish ***
Cheng Wang, Shuaipeng He, Dan Li, Biao Zhang, Yu Dai, Can Li, Xuan Li, Le Kang, Shujun Yang, Su Zhang, Ning Fan, Hong Chang, Gongjin Wu, Zhongjin Yue, Junhai Ma, Panfeng Shang
Department of Urology, The Second Hospital of Lanzhou University, Lanzhou, Gansu, China., Lanzhou University, Lanzhou, Gansu, China.